1. Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines.
- Author
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Kang, Yanliang, Zhang, Wanli, Yu, Qiumin, Gao, Le, Quan, Jiale, Gu, Fangling, Wu, Yuxin, Tian, Yahong, Wu, Zijie, Shao, Shishuai, Zhou, Hongyou, Duan, Shukang, Zhou, Yixiang, Zhang, Li, Gao, Xiangdong, Tian, Hong, and Yao, Wenbing
- Subjects
T helper cells ,DNA folding ,CANCER vaccines ,T cells ,CARCINOGENESIS ,CYTOTOXIC T cells - Abstract
Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4
+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+ T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2023
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